PROJECT SUMMARY We will investigate the neural substrates of the maturation of response inhibition between the time of adolescence and adulthood. Response inhibition is thought to be mediated by the prefrontal cortex, a cortical area greatly expanded in primates compared to other vertebrates, which undergoes a long maturation process that mirrors the development of higher cognitive functions after adolescence. A number of mental illnesses have onsets linked to the maturation of the prefrontal cortex, most notably schizophrenia, which manifests itself in early adulthood. Executive function also improves in adulthood, and inadequate development of this capacity is associated with delinquency and other conditions of health and social significance. Little is known about the physiological changes that the prefrontal cortex undergoes in adolescence so as to mediate improved cognitive control. Taking advantage of recent methodological and conceptual advances, we propose to investigate the changes of prefrontal cortical physiology and anatomical connectivity that occur after puberty. We propose to use a non-human primate model that will allow us to conduct behavioral assessments, neurophysiological recordings, and MR imaging in the prefrontal cortex of developing animals and controls. Our study will make use behavioral tasks that test response inhibition. We will rely primarily on the anti-saccade task which requires subjects to make an eye movement in the opposite direction of a visual stimulus, thus resisting the pre-potent stimulus. Experiments will record neuronal activity related to task performance to understand what neural variables maturate after the onset of puberty. These experiments will offer insights on how development of the prefrontal cortex alters its physiological responses, findings that will be essential for understanding and treating mental illnesses thought to be associated with a failure of prefrontal cortical maturation.